Efficacy of anidulafungin in 539 patients with invasive candidiasis: a patient-level pooled analysis of six clinical trials

Bart Jan Kullberg, José Vasquez, Piroon Mootsikapun, Marcio Nucci, José-Artur Paiva, Jorge Garbino, Jean Li Yan, Jalal Aram, Maria Rita Capparella, Umberto Conte, Haran Schlamm, Robert Swanson, Raoul Herbrecht, Bart Jan Kullberg, José Vasquez, Piroon Mootsikapun, Marcio Nucci, José-Artur Paiva, Jorge Garbino, Jean Li Yan, Jalal Aram, Maria Rita Capparella, Umberto Conte, Haran Schlamm, Robert Swanson, Raoul Herbrecht

Abstract

Objectives: To evaluate the efficacy of anidulafungin for the treatment of candidaemia and invasive candidiasis in a large dataset, including patients with deep-seated tissue candidiasis, neutropenia and infection due to non- albicans Candida species.

Methods: Data were pooled from six prospective, multicentre, multinational studies: four open-label, non-comparative studies of anidulafungin and two double-blind, double-dummy, randomized studies of anidulafungin versus caspofungin (clinical trial registrations: NCT00496197, NCT00548262, NCT00537329, NCT00689338, NCT00806351 and NCT00805740; ClinicalTrials.gov). In all studies, patients with culture-confirmed invasive candidiasis received a single intravenous (iv) loading dose of anidulafungin 200 mg on day 1, followed by 100 mg once-daily. Switch to oral fluconazole or voriconazole was permitted after 5-10 days of iv treatment in all studies except one. Antifungal treatment (iv plus oral therapy if applicable) was maintained for ≥14 days after the last positive Candida culture. The primary endpoint was successful global response at end of iv therapy (EOivT) in the modified ITT (mITT) population.

Results: In total, 539 patients were included (mITT population). The most common baseline Candida species were Candida albicans (47.9%), Candida glabrata (21.0%), Candida tropicalis (13.7%), Candida parapsilosis (13.2%) and Candida krusei (3.5%). Median duration of anidulafungin iv treatment was 10.0 days. The global response success rate at EOivT was 76.4% (95% CI 72.9%-80.0%). All-cause mortality was 13.0% on day 14 and 19.1% on day 28. Adverse events (AEs) were consistent with the known AE profile for anidulafungin.

Conclusions: These data demonstrate that anidulafungin is effective for treatment of candidaemia and invasive candidiasis in a broad patient population.

© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Figures

Figure 1
Figure 1
Patient disposition. AE, adverse event; C/IC, candidaemia or invasive candidiasis; mITT, modified ITT. aPatients who completed all visits as described in the respective protocols. bIn the period from the first dose of study medication until the end of study follow-up visit.
Figure 2
Figure 2
(a) Global, clinical and microbiological response success rates in all patients at end of intravenous therapy (EOivT); and (b) global response success rates at EOivT in patients with deep-seated tissue infection and neutropenic patients (mITT population).
Figure 3
Figure 3
Global response success rates at end of intravenous therapy stratified by main baseline pathogen (patients could have more than one Candida species at baseline) in (a) all patients, (b) patients with deep-seated tissue candidiasis and (c) neutropenic patients.

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